The objectives of this research project are to study the interaction of nucleic acids with anticancer durgs, antiviral agents and interferon inducers, and to obtain a clearer understanding of the stereochemistry and the structural concepts of drug-nucleic acid interactions by using a combined approach of solution spectroscopic studies in conjunction with the techniques of molecular co-crystallization and X-ray diffraction analysis. Among the numerous drugs and antibiotics which exert their pharmacological activity by direct interaction with nucleic acid, compounds such as tilorone hydrochloride and particularly its fluoranthene derivative exhibit a diverse range of antitumor, antiviral and interferon inducing activity. Our solution spectroscopic studies of complexes of DEAP-fluoranthene with self-complementary ribodinucleoside monophosphates and deoxydinucleotides indicate the possibility of both base and sequence DNA and RNA template selectivity. Information from these solution studies in conjunction with the molecular co-crystallization techniques has led to the successful co-crystallization of DEAP-fluoranthene with two ribodinucleoside monophosphates (CpG and UpA) and with two deoxydinucleotides (pdApdT and dTpdA). X-ray diffraction analyses of these four fluoranthene-nucleic acid crystalline complexes are currently in progress. This research proposal describes further work on the studies of fluoranthene-oligonucleotide complexes. Combined information on both the solid state and solution complexes of these compounds with nucleic acids (dinucleotides and oligonucleotides) may lead to a better understanding of the mechanisms of drug-nucleic acid interactions; these studies may also provide useful information for the rational design of more effective anticancer drugs, antiviral agents and interferon inducers.